Kuraishi Yasushi, Takasaki Ichiro, Nojima Hiroshi, Shiraki Kimiyasu, Takahata Hiroki
Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Life Sci. 2004 Apr 9;74(21):2619-26. doi: 10.1016/j.lfs.2004.01.005.
The inoculation of mice with herpes simplex virus type-1 (HSV-1) causes herpes zoster-like skin lesions and pain-related responses (tactile allodynia and mechanical hyperalgesia) from day 5 after inoculation. Skin lesions completely heal by day 15 after inoculation, but about half of mice with acute herpetic pain show pain-related responses long after the lesions heal. Using this mouse model, we examined the effects of repeated administration of gabapentin and amitriptyline on the acute herpetic pain and the incidence of postherpetic pain. Gabapentin and amitriptyline were administered three times daily from day 5 to 11 after inoculation. Postherpetic pain-related responses were assessed on day 30 after inoculation. Gabapentin (10-100 mg/kg) produced the dose-dependent inhibition of acute herpetic pain-related responses. This medication produced marked reduction in the incidence of delayed postherpetic pain and the dose of 100 mg/kg produced the complete inhibition. Amitriptyline (10 mg/kg) did not affect the acute pain-related responses in the initial 3- and 2-day periods and then gradually inhibited them. This dosage produced a substantial but non-significant decrease in the incidence of postherpetic pain-related responses. Amitriptyline (1 and 3 mg/kg) was without effects on acute herpetic and postherpetic pain-related responses. The results strongly support the idea that the severity of the acute herpetic pain is a risk factor of postherpetic neuralgia. It may be worth testing the effects of gabapentin on acute herpetic pain and the incidence of postherpetic neuralgia in human subjects.
用1型单纯疱疹病毒（HSV-1）接种小鼠，从接种后第5天开始会引发带状疱疹样皮肤损伤以及与疼痛相关的反应（触觉异常性疼痛和机械性痛觉过敏）。接种后第15天皮肤损伤完全愈合，但约一半患有急性疱疹性疼痛的小鼠在损伤愈合后很长时间仍表现出与疼痛相关的反应。利用这个小鼠模型，我们研究了反复给予加巴喷丁和阿米替林对急性疱疹性疼痛及疱疹后神经痛发生率的影响。从接种后第5天至第11天，每天三次给予加巴喷丁和阿米替林。在接种后第30天评估疱疹后与疼痛相关的反应。加巴喷丁（10 - 100毫克/千克）对急性疱疹性疼痛相关反应产生剂量依赖性抑制作用。这种药物使延迟性疱疹后神经痛的发生率显著降低，100毫克/千克的剂量产生完全抑制作用。阿米替林（10毫克/千克）在最初的3天和2天内对急性疼痛相关反应没有影响，然后逐渐抑制它们。该剂量使疱疹后疼痛相关反应的发生率大幅降低但无统计学意义。阿米替林（1毫克/千克和3毫克/千克）对急性疱疹性和疱疹后疼痛相关反应没有影响。结果有力地支持了急性疱疹性疼痛的严重程度是疱疹后神经痛危险因素这一观点。在人类受试者中测试加巴喷丁对急性疱疹性疼痛及疱疹后神经痛发生率的影响可能是值得的。
